It is well established that an intact sensory neural supply is essential to the maintenance of normal corneal health. Corneal nerves play a role in mitogenesis of the corneal epithelium and corneal epithelial wound healing. The mechanism(s) whereby they exert their influence is poorly defined. It is suggested that the release of neuropeptides play an essential role in the trophic influences of the nerve supply on corneal trophic and reparative processes. Preliminary data is presented which suggests the neuropeptide substance P (SP) to influence corneal epithelial cell migration, cell adhesion and mitogenesis and decreased SP to be associated with corneal disease. It is possible that the alteration of neuropeptide content represents the common underlying defect in diverse corneal wound healing disorders including diabetic keratopathy, metaherpetic keratitis, recurrent epithelial erosions and delayed healing associated with thermal and alkali burns as well as post corneal transplant. In this application five hypotheses will be tested using a combination of in vitro and animal experiments. 1. SP is necessary for the maintenance of corneal health and corneal epithelial wound healing. 2. Decreased availability of SP impairs corneal epithelial wound healing in diabetic and galactosemic animals. 3. Neuropeptides play a role in corneal epithelial migration during the wound healing process. 4. Neuropeptides play a role in the development and maintenance of corneal epithelial cell adhesion. 5. SP content is modulated in canine patients that have spontaneously occurring chronic non-septic corneal epithelial defects. The long term goals of this research are to better understand the roles of neuropeptides in maintenance of corneal health and in corneal disease states with a view towards their possible application in the treatment of corneal epithelial wound healing disorders which are seen in human and veterinary patients.